Protein hydrolysates are specific protein fragments, produced during enzymatic hydrolysis and can exert various biological functions. The present study investigated the acute toxicity study of protein hydrolysates derived from black tilapia (Oreochromis placidus) and their effect on hypertensive-induced mice. Protein hydrolysates were produced from black tilapia protein isolate through enzymatic hydrolysis. A single dose of protein hydrolysates at 2000 mg/kg of body weight was administered and any changes were observed for 14 days. During 14 days, there were no significant changes in liver enzyme content and kidney function content, adverse clinical signs and mortality. The effect of the administration of protein hydrolysates in hypertensive-induced mice was studied. The body weight, blood pressure, full blood count {red blood cell (RBC), white blood cell (WBC) and platelets} were observed. Hypertensive mice (systolic blood pressure; 161±3 mm/Hg) were fed with pellet consisting of protein hydrolysates at different concentrations as well as carvedilol and combination of carvedilol and protein hydrolysates and systolic blood pressure was monitored. After 28 days, there was a significant reduction of blood pressure in the group of carvedilol (107±4 mm/Hg), 5% protein hydrolysate (119±1 mm/ Hg), 10% protein hydrolysate (123±1 mm/Hg), 20% protein hydrolysate (115±2 mm/Hg) and 10% protein hydrolysate in combination with carvedilol (103±2 mm/Hg). Red blood cells significantly increased in hypertension mice but no significant changes in white blood cells and platelets after 28 days. Administration of protein hydrolysates reduced red blood cell levels similar to control group. A significant increase in body weight was observed in hypertension mice administered with protein hydrolysates at different concentrations as well as carvedilol and a combination of carvedilol and protein hydrolysates compared to control group and hypertensive group. Studies on any changes in liver enzyme level, kidney function level and angiotensin converting enzyme (ACE) activity on blood serum were carried out. Results showed that treatment with protein hydrolysates on hypertensive-induced mice reduced liver enzyme levels (ALP, ALT and GGT) and kidney function levels (Na+, K+ and Cl-) to normal levels. ACE enzyme activity of hypertensive-induced mice in the serum was also reduced similar to control mice after being treated with protein hydrolysates.